Displaying publications 1 - 20 of 36 in total

  1. Hagen RM, Adamo P, Karamat S, Oxley J, Aning JJ, Gillatt D, et al.
    Am J Clin Pathol, 2014 Oct;142(4):533-40.
    PMID: 25239421 DOI: 10.1309/AJCPH88QHXARISUP
    The proto-oncogene ETS-related gene (ERG) is consistently overexpressed in prostate cancer. Alternatively spliced isoforms of ERG have variable biological activities; inclusion of exon 11 (72 base pairs [bp]) is associated with aggressiveness and progression of disease. Exon 10 (81 bp) has also been shown to be alternatively spliced. Within this study, we assess whether ERG protein, messenger RNA (mRNA), and ERG splice isoform mRNA expression is altered as prostate cancer progresses.
    Matched MeSH terms: Exons/genetics
  2. Hamanaka K, Imagawa E, Koshimizu E, Miyatake S, Tohyama J, Yamagata T, et al.
    Am J Hum Genet, 2020 04 02;106(4):549-558.
    PMID: 32169168 DOI: 10.1016/j.ajhg.2020.02.011
    De novo variants (DNVs) cause many genetic diseases. When DNVs are examined in the whole coding regions of genes in next-generation sequencing analyses, pathogenic DNVs often cluster in a specific region. One such region is the last exon and the last 50 bp of the penultimate exon, where truncating DNVs cause escape from nonsense-mediated mRNA decay [NMD(-) region]. Such variants can have dominant-negative or gain-of-function effects. Here, we first developed a resource of rates of truncating DNVs in NMD(-) regions under the null model of DNVs. Utilizing this resource, we performed enrichment analysis of truncating DNVs in NMD(-) regions in 346 developmental and epileptic encephalopathy (DEE) trios. We observed statistically significant enrichment of truncating DNVs in semaphorin 6B (SEMA6B) (p value: 2.8 × 10-8; exome-wide threshold: 2.5 × 10-6). The initial analysis of the 346 individuals and additional screening of 1,406 and 4,293 independent individuals affected by DEE and developmental disorders collectively identified four truncating DNVs in the SEMA6B NMD(-) region in five individuals who came from unrelated families (p value: 1.9 × 10-13) and consistently showed progressive myoclonic epilepsy. RNA analysis of lymphoblastoid cells established from an affected individual showed that the mutant allele escaped NMD, indicating stable production of the truncated protein. Importantly, heterozygous truncating variants in the NMD(+) region of SEMA6B are observed in general populations, and SEMA6B is most likely loss-of-function tolerant. Zebrafish expressing truncating variants in the NMD(-) region of SEMA6B orthologs displayed defective development of brain neurons and enhanced pentylenetetrazole-induced seizure behavior. In summary, we show that truncating DNVs in the final exon of SEMA6B cause progressive myoclonic epilepsy.
    Matched MeSH terms: Exons/genetics*
  3. Chua EW, Miller AL, Kennedy MA
    Anal Biochem, 2015 May 15;477:115-7.
    PMID: 25766577 DOI: 10.1016/j.ab.2015.02.023
    We compared four brands of microtubes with respect to their suitability for long-range polymerase chain reactions (PCRs). One of the four brands was found to have an inhibitory effect, decreasing PCR yields. The effect was universal across different PCR or enzyme systems. Increased ultraviolet absorbance suggests leaching of unknown chemical species into PCR mixtures. However, this could not be confirmed by high-performance liquid chromatography-mass spectrometry analysis. Nevertheless, our article demonstrates a clear impact of the choice of microtubes on long-range PCR success. Due consideration should be given to the PCR microtubes when determining optimal reaction conditions for long-range PCR.
    Matched MeSH terms: Exons/genetics
  4. Tay YW, Lim JL, Tan AH, Annuar AA, Lim SY
    Ann Acad Med Singap, 2021 04;50(4):353-355.
    PMID: 33990826 DOI: 10.47102/annals-acadmedsg.2020508
    Matched MeSH terms: Exons/genetics
  5. Ibrahim IK, Hassan R, Ali EW, Omer A
    Asian Pac J Cancer Prev, 2019 Jan 25;20(1):41-44.
    PMID: 30677867
    Background: In recent years, a somatic point mutation in the Janus Kinase 2 (JAK2) gene (1849 G→T, V617F)
    has been reported to occur in over 90% of patients with polycythemia vera (PV). Another JAK2 mutation in exon 12
    had been described and shown capable of activating erythropoietin signaling pathways. Objective: In this study, we
    aimed to determine the frequency of Jak2 mutations (JAK2V617F and JAK2 exon 12) as well as their relationships
    with hematological parameters in Sudanese patients with myeloproliferative disorders (MPD). A comparison with
    findings of published studies from other geographic regions was included. Materials and Methods: From each of
    a total of 83 polycythaemia patients, six milliliters (ml) of venous blood were collected and processed for molecular
    analysis and measurement of serum erythropoietin level by enzyme-linked immunoassay (ELISA). The JAK2 V617F
    mutation was determined using an allele-specific competitive blocker (ACB) -PCR assay and High Resolution Melting
    (HRM) analysis was applied for the JAK2 exon 12 mutation. Results: According to patients’ history and the results
    for EPO levels, nine (10.7 %) out of 83 patients were found to have secondary polycythaemia and 74 (89.3%) PV. The
    overall frequency of the 2 JAK2 mutations was 94.6% in our Sudanese PV patients, JAK2V617F being found in 91%
    and JAK2 exon 12 mutations in 8.1%.Conclusion: In summary JAK2 V617F and JAK2 exon 12 mutations are very
    common in Sudanese PC cases.
    Matched MeSH terms: Exons/genetics*
  6. Chan KL, Rosli R, Tatarinova TV, Hogan M, Firdaus-Raih M, Low EL
    BMC Bioinformatics, 2017 Jan 27;18(Suppl 1):1426.
    PMID: 28466793 DOI: 10.1186/s12859-016-1426-6
    BACKGROUND: Gene prediction is one of the most important steps in the genome annotation process. A large number of software tools and pipelines developed by various computing techniques are available for gene prediction. However, these systems have yet to accurately predict all or even most of the protein-coding regions. Furthermore, none of the currently available gene-finders has a universal Hidden Markov Model (HMM) that can perform gene prediction for all organisms equally well in an automatic fashion.

    RESULTS: We present an automated gene prediction pipeline, Seqping that uses self-training HMM models and transcriptomic data. The pipeline processes the genome and transcriptome sequences of the target species using GlimmerHMM, SNAP, and AUGUSTUS pipelines, followed by MAKER2 program to combine predictions from the three tools in association with the transcriptomic evidence. Seqping generates species-specific HMMs that are able to offer unbiased gene predictions. The pipeline was evaluated using the Oryza sativa and Arabidopsis thaliana genomes. Benchmarking Universal Single-Copy Orthologs (BUSCO) analysis showed that the pipeline was able to identify at least 95% of BUSCO's plantae dataset. Our evaluation shows that Seqping was able to generate better gene predictions compared to three HMM-based programs (MAKER2, GlimmerHMM and AUGUSTUS) using their respective available HMMs. Seqping had the highest accuracy in rice (0.5648 for CDS, 0.4468 for exon, and 0.6695 nucleotide structure) and A. thaliana (0.5808 for CDS, 0.5955 for exon, and 0.8839 nucleotide structure).

    CONCLUSIONS: Seqping provides researchers a seamless pipeline to train species-specific HMMs and predict genes in newly sequenced or less-studied genomes. We conclude that the Seqping pipeline predictions are more accurate than gene predictions using the other three approaches with the default or available HMMs.

    Matched MeSH terms: Exons/genetics
  7. Saleh MA, Solayman M, Paul S, Saha M, Khalil MI, Gan SH
    Biomed Res Int, 2016;2016:9142190.
    PMID: 27294143 DOI: 10.1155/2016/9142190
    Despite the reported association of adiponectin receptor 1 (ADIPOR1) gene mutations with vulnerability to several human metabolic diseases, there is lack of computational analysis on the functional and structural impacts of single nucleotide polymorphisms (SNPs) of the human ADIPOR1 at protein level. Therefore, sequence- and structure-based computational tools were employed in this study to functionally and structurally characterize the coding nsSNPs of ADIPOR1 gene listed in the dbSNP database. Our in silico analysis by SIFT, nsSNPAnalyzer, PolyPhen-2, Fathmm, I-Mutant 2.0, SNPs&GO, PhD-SNP, PANTHER, and SNPeffect tools identified the nsSNPs with distorting functional impacts, namely, rs765425383 (A348G), rs752071352 (H341Y), rs759555652 (R324L), rs200326086 (L224F), and rs766267373 (L143P) from 74 nsSNPs of ADIPOR1 gene. Finally the aforementioned five deleterious nsSNPs were introduced using Swiss-PDB Viewer package within the X-ray crystal structure of ADIPOR1 protein, and changes in free energy for these mutations were computed. Although increased free energy was observed for all the mutants, the nsSNP H341Y caused the highest energy increase amongst all. RMSD and TM scores predicted that mutants were structurally similar to wild type protein. Our analyses suggested that the aforementioned variants especially H341Y could directly or indirectly destabilize the amino acid interactions and hydrogen bonding networks of ADIPOR1.
    Matched MeSH terms: Exons/genetics
  8. Alhasan AA, Izuogu OG, Al-Balool HH, Steyn JS, Evans A, Colzani M, et al.
    Blood, 2016 Mar 03;127(9):e1-e11.
    PMID: 26660425 DOI: 10.1182/blood-2015-06-649434
    In platelets, splicing and translation occur in the absence of a nucleus. However, the integrity and stability of mRNAs derived from megakaryocyte progenitor cells remain poorly quantified on a transcriptome-wide level. As circular RNAs (circRNAs) are resistant to degradation by exonucleases, their abundance relative to linear RNAs can be used as a surrogate marker for mRNA stability in the absence of transcription. Here we show that circRNAs are enriched in human platelets 17- to 188-fold relative to nucleated tissues and 14- to 26-fold relative to samples digested with RNAse R to selectively remove linear RNA. We compare RNAseq read depths inside and outside circRNAs to provide in silico evidence of transcript circularity, show that exons within circRNAs are enriched on average 12.7 times in platelets relative to nucleated tissues and identify 3162 genes significantly enriched for circRNAs, including some where all RNAseq reads appear to be derived from circular molecules. We also confirm that this is a feature of other anucleate cells through transcriptome sequencing of mature erythrocytes, demonstrate that circRNAs are not enriched in cultured megakaryocytes, and demonstrate that linear RNAs decay more rapidly than circRNAs in platelet preparations. Collectively, these results suggest that circulating platelets have lost >90% of their progenitor mRNAs and that translation in platelets occurs against the backdrop of a highly degraded transcriptome. Finally, we find that transcripts previously classified as products of reverse transcriptase template switching are both enriched in platelets and resistant to decay, countering the recent suggestion that up to 50% of rearranged RNAs are artifacts.
    Matched MeSH terms: Exons/genetics
  9. Aslam S, Yee VC, Narayanan S, Duraisamy G, Standen GR
    Br J Haematol, 1997 Aug;98(2):346-52.
    PMID: 9266932
    Molecular analysis has been performed on a Malaysian patient with a severe bleeding disorder due to factor XIII(A) subunit deficiency. Total mRNA was isolated from the patient's leucocytes and four overlapping segments corresponding to the entire coding region of the A subunit cDNA were amplified by RT-PCR. The cDNA segments amplified efficiently and were of expected size. Direct sequencing of the complete reading frame revealed a single homozygous base change (nt 1327G-T) in exon 10 corresponding to a missense mutation, Val414Phe, in the catalytic core domain of the A subunit monomer. The mutation eliminates a BsaJ1 restriction site and family screening showed that both parents were heterozygous for the defect. The base substitution was absent in 55 normal individuals. Val414 is a highly conserved residue in the calcium-dependent transglutaminase enzyme family. Computer modelling based on 3D crystallographic data predicts that the bulky aromatic side chain of the substituted phenylalanine residue distorts protein folding and destabilizes the molecule. In addition, conformation changes in the adjacent catalytic and calcium binding regions of the A subunit are likely to impair the enzymatic activity of any protein synthesized.
    Matched MeSH terms: Exons/genetics
  10. Mohamed Z, Ahmad R, Yoke NS, Zakaria Z, Ahmad H, Yew TH
    Cancer Sci, 2003 Aug;94(8):725-8.
    PMID: 12901799 DOI: 10.1111/j.1349-7006.2003.tb01509.x
    The present study was carried out to characterize the causative genetic mutation in a medium-sized Malaysian Chinese pedigree of three generations affected with familial adenomatous polyposis (FAP). Clinical data and genetic studies revealed considerable phenotypic variability in affected individuals in this family. Blood was obtained from members of the FAP-01 family and genomic DNA was extracted. Mutation screening of the adenomatous polyposis coli (APC) gene was carried out using the single strand conformation polymorphism (SSCP) technique. The possibility of exon skipping was predicted by splicing motif recognition software (ESEfinder release2.0). SSCP results showed mobility shifts in exon 8 of the APC gene which segregated with affected members of the family. Sequence analysis revealed that the affected individuals are heterozygous for a C847T transition, whilst all the unaffected family members and control individuals are homozygous C at the same position. This nucleotide substitution generates a stop codon at amino acid position 283, in place of the usual arginine (Arg283Ter). We conclude that an Arg283Ter mutation in the APC gene is causative of the FAP phenotype in this family, although there is considerable variation in the presentation of this disease among affected individuals. Computational analysis predicts that this mutation occurs within sequences that may function as splicing signals, so that the sequence change may affect normal splicing.
    Matched MeSH terms: Exons/genetics*
  11. Hasmad HN, Sivanandan K, Lee V, Yip CH, Mohd Taib NA, Teo SH
    Clin Genet, 2015 Apr;87(4):392-4.
    PMID: 25066186 DOI: 10.1111/cge.12451
    Matched MeSH terms: Exons/genetics
  12. Saharudin S, Sanusi SY, Ponnuraj KT
    Clin Oral Investig, 2022 Feb;26(2):1261-1268.
    PMID: 34453594 DOI: 10.1007/s00784-021-04098-x
    OBJECTIVE: The aim of this study is to do a sequencing analysis of RUNX2 in non-syndromic patients with supernumerary tooth.

    MATERIALS AND METHODS: Fifty-three patients with supernumerary tooth were identified retrospectively from 1,275 radiographic reviews who attended the Hospital Universiti Sains Malaysia (USM) Dental Clinic. Informed consent was obtained from the patients prior to the study. Blood samples were collected from 41 patients and DNA extractions were performed out of which 10 samples were chosen randomly for PCR amplification using designated primers for RUNX2 followed by DNA sequencing analysis.

    RESULTS: This study involved 28 male patients (68.3%) and 13 female patients (31.7%) with a gender ratio of 2.2:1 and mean age of 15.9 ± 6.2 years. DNA extraction yielded ~ 40 ng/μl of concentrated DNA, and each DNA sample had more than 1500 bp of DNA length. The purity ranged between 1.8 and 2.0. DNA sequencing analysis did not reveal any mutations in exons 5 and 6 of RUNX2.

    CONCLUSION: This study did not reveal any mutations in exons 5 and 6 of RUNX2 in non-syndromic patients with supernumerary tooth.

    CLINICAL RELEVANCE: Analysis of mutations in RUNX2 is important to enhance the understanding of tooth development in humans.

    Matched MeSH terms: Exons/genetics
  13. Jorquera R, González C, Clausen P, Petersen B, Holmes DS
    Database (Oxford), 2018 01 01;2018:1-6.
    PMID: 30239665 DOI: 10.1093/database/bay089
    Efficient extraction of knowledge from biological data requires the development of structured vocabularies to unambiguously define biological terms. This paper proposes descriptions and definitions to disambiguate the term 'single-exon gene'. Eukaryotic Single-Exon Genes (SEGs) have been defined as genes that do not have introns in their protein coding sequences. They have been studied not only to determine their origin and evolution but also because their expression has been linked to several types of human cancer and neurological/developmental disorders and many exhibit tissue-specific transcription. Unfortunately, the term 'SEGs' is rife with ambiguity, leading to biological misinterpretations. In the classic definition, no distinction is made between SEGs that harbor introns in their untranslated regions (UTRs) versus those without. This distinction is important to make because the presence of introns in UTRs affects transcriptional regulation and post-transcriptional processing of the mRNA. In addition, recent whole-transcriptome shotgun sequencing has led to the discovery of many examples of single-exon mRNAs that arise from alternative splicing of multi-exon genes, these single-exon isoforms are being confused with SEGs despite their clearly different origin. The increasing expansion of RNA-seq datasets makes it imperative to distinguish the different SEG types before annotation errors become indelibly propagated in biological databases. This paper develops a structured vocabulary for their disambiguation, allowing a major reassessment of their evolutionary trajectories, regulation, RNA processing and transport, and provides the opportunity to improve the detection of gene associations with disorders including cancers, neurological and developmental diseases.
    Matched MeSH terms: Exons/genetics*
  14. Song BK, Hein I, Druka A, Waugh R, Marshall D, Nadarajah K, et al.
    Funct. Integr. Genomics, 2009 Feb;9(1):97-108.
    PMID: 18633654 DOI: 10.1007/s10142-008-0091-x
    Common wild rice (Oryza rufipogon) plays an important role by contributing to modern rice breeding. In this paper, we report the sequence and analysis of a 172-kb genomic DNA region of wild rice around the RM5 locus, which is associated with the yield QTL yld1.1. Comparative sequence analysis between orthologous RM5 regions from Oryza sativa ssp. japonica, O. sativa ssp. indica and O. rufipogon revealed a high level of conserved synteny in the content, homology, structure, orientation, and physical distance of all 14 predicted genes. Twelve of the putative genes were supported by matches to proteins with known function, whereas two were predicted by homology to rice and other plant expressed sequence tags or complementary DNAs. The remarkably high level of conservation found in coding, intronic and intergenic regions may indicate high evolutionary selection on the RM5 region. Although our analysis has not defined which gene(s) determine the yld1.1 phenotype, allelic variation and the insertion of transposable elements, among other nucleotide changes, represent potential variation responsible for the yield QTL. However, as suggested previously, two putative receptor-like protein kinase genes remain the key suspects for yld1.1.
    Matched MeSH terms: Exons/genetics
  15. Chua KH, Ng CC, Hilmi I, Goh KL
    Genet. Mol. Res., 2012;11(3):3115-21.
    PMID: 23007989
    Crohn's disease is a chronic, relapsing inflammatory bowel disease; it affects the mucosa and deeper layers of the digestive wall. Two Crohn's disease patients who carried the JW1 variant and two patients who carried the SNP5 variant were investigated for other co-inherited polymorphisms that could influence Crohn's disease development. Based on the sequencing results, a homozygous 5'-UTR-59 G to A variant in exon 1 (SNP6) was observed in a patient who carried SNP5, while a heterozygous SNP6 variant was detected in the other patient who carried SNP5. No other associated mutations or polymorphisms were detected in the two patients who carried the JW1 variant of the CARD15/NOD2 gene.
    Matched MeSH terms: Exons/genetics
  16. Kaur A, Cho L, Cereb N, Lin PY, Yang KL
    HLA, 2020 09;96(3):329-330.
    PMID: 32227684 DOI: 10.1111/tan.13884
    One nucleotide substitution in codon 73 of HLA-A*01:01:01:01 results in a novel allele, HLA-A*01:211.
    Matched MeSH terms: Exons/genetics
  17. Cho L, Kaur A, Cereb N, Lin PY, Yang KL
    HLA, 2020 09;96(3):344-345.
    PMID: 32212215 DOI: 10.1111/tan.13879
    One nucleotide substitution in codon 112 of HLA-B*15:349:01 results in a novel allele, HLA-B*15:349:02.
    Matched MeSH terms: Exons/genetics
  18. Cho L, Kaur A, Cereb N, Lin PY, Yang KL
    HLA, 2020 08;96(2):243-244.
    PMID: 32250029 DOI: 10.1111/tan.13889
    One nucleotide substitution in codon 38 of HLA-DQB1*06:01:01:01 results in a novel allele, HLA-DQB1*06:132.
    Matched MeSH terms: Exons/genetics
  19. Cho L, Kaur A, Cereb N, Lin PY, Yang KL
    HLA, 2020 08;96(2):240-241.
    PMID: 32246584 DOI: 10.1111/tan.13887
    Nucleotide substitutions in codon 38 of HLA-DQB1*05:03:01:01 result in a novel allele, HLA-DQB1*05:66:01.
    Matched MeSH terms: Exons/genetics
  20. Cho L, Kaur A, Cereb N, Lin PY, Yang KL
    HLA, 2020 08;96(2):217-218.
    PMID: 32227685 DOI: 10.1111/tan.13873
    One nucleotide substitution in codon 89 of HLA-B*38:02:01:01 results in a novel allele, HLA-B*38:64.
    Matched MeSH terms: Exons/genetics
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